Lifestyle and Metabolic Effects on Erectile, Vascular Health
Lifestyle and Metabolic Effects on Erectile, Vascular Health
Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.
It is remarkable that a compound as unstable as nitric oxide (NO) evolved as the critical factor determining the capacity for an erection, and therefore perpetuation of our species. NO lasts only a few seconds in tissues due to its unbalanced electrons, and its production and stability depend on extensive antioxidant protection.
Antioxidant defenses are reduced in men with ED. In a study of levels of reduced glutathione (GSH), an important intracellular antioxidant, men with and without diabetes had significant decreases of GSH if they also had ED (1931±581 versus 2269±232 and 1671±438 versus 2084±118, mean±s.d. (μmol l), respectively, both P<0.001); diabetic men, as expected, had significantly lower levels than men without diabetes (Figure 1). In a study of young men with ED, serum levels of paraoxonase-1 activity were markedly lower (mean±s.d. 119±62 versus 185±56, P<0.001) compared with men without ED. Both low paraoxonase-1 activity and low high-density lipoprotein (HDL) cholesterol were independent predictors of ED in this population. Paraoxonase-1 is an HDL cholesterol-associated circulating antioxidant enzyme that appears to at least partially mediate many positive and negative atherogenic factors. These lower levels of both cellular and circulating antioxidants in men with ED are most likely due to oxidative stress and/or low antioxidant intake, rather than to inherent abnormalities of antioxidant protection. Oxidative stress and inflammatory factors such as C-reactive protein are increased in men with ED.
(Enlarge Image)
Figure 1.
Red blood cell glutathione concentrations (μmol l) in 111 men with ED: 64 with diabetes mellitus (ED/DM); 47 without diabetes mellitus (ED/wDM); 20 diabetic subjects (DM) and 26 normal subjects (C). Adapted with permission.
ED is associated with reduced NO production in the systemic vasculature. In normal weight men, mean±s.e. flow-mediated dilation (FMD) was 2.4±0.21% in the men with ED compared with 3.9±0.26% in the men without ED (P<0.001). This review will discuss various lifestyle and metabolic factors influencing vascular NO and erectile function, with an emphasis on the role of oxidative stress and inflammation, and specific interventions available to maximize erectile and vascular health.
Abstract and Introduction
Abstract
Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.
Introduction
It is remarkable that a compound as unstable as nitric oxide (NO) evolved as the critical factor determining the capacity for an erection, and therefore perpetuation of our species. NO lasts only a few seconds in tissues due to its unbalanced electrons, and its production and stability depend on extensive antioxidant protection.
Antioxidant defenses are reduced in men with ED. In a study of levels of reduced glutathione (GSH), an important intracellular antioxidant, men with and without diabetes had significant decreases of GSH if they also had ED (1931±581 versus 2269±232 and 1671±438 versus 2084±118, mean±s.d. (μmol l), respectively, both P<0.001); diabetic men, as expected, had significantly lower levels than men without diabetes (Figure 1). In a study of young men with ED, serum levels of paraoxonase-1 activity were markedly lower (mean±s.d. 119±62 versus 185±56, P<0.001) compared with men without ED. Both low paraoxonase-1 activity and low high-density lipoprotein (HDL) cholesterol were independent predictors of ED in this population. Paraoxonase-1 is an HDL cholesterol-associated circulating antioxidant enzyme that appears to at least partially mediate many positive and negative atherogenic factors. These lower levels of both cellular and circulating antioxidants in men with ED are most likely due to oxidative stress and/or low antioxidant intake, rather than to inherent abnormalities of antioxidant protection. Oxidative stress and inflammatory factors such as C-reactive protein are increased in men with ED.
(Enlarge Image)
Figure 1.
Red blood cell glutathione concentrations (μmol l) in 111 men with ED: 64 with diabetes mellitus (ED/DM); 47 without diabetes mellitus (ED/wDM); 20 diabetic subjects (DM) and 26 normal subjects (C). Adapted with permission.
ED is associated with reduced NO production in the systemic vasculature. In normal weight men, mean±s.e. flow-mediated dilation (FMD) was 2.4±0.21% in the men with ED compared with 3.9±0.26% in the men without ED (P<0.001). This review will discuss various lifestyle and metabolic factors influencing vascular NO and erectile function, with an emphasis on the role of oxidative stress and inflammation, and specific interventions available to maximize erectile and vascular health.